Modeling Hedonic Processing and Anhedonia in Depression

描述（由申请人提供）：快感缺乏，或缺乏积极情绪，是抑郁症的一个重要组成部分，在诊断标准中以各种方式表现出来。所有形式的抑郁症都可能涉及对活动缺乏兴趣或乐趣，特别是当抑郁症患者与健康对照时。与非典型抑郁症不同，忧郁性抑郁症特别需要对愉快事件的情绪反应的额外缺陷，而非典型抑郁症对愉快事件的情绪反应是存在的。与NIMH的战略目标1一致，本申请旨在以一种理论上连贯的方式评估快感缺乏症，并通过旨在评估抑郁症中各种快感缺乏症处理的任务，解决抑郁症中欲望、喜好和学习方面的缺陷。在每个任务中，在愉快和中性条件下，耳后反射和颧肌电图的大小将被评估为积极情绪处理的测量。研究人员将评估惊视眨眼和皱襞肌肌电图的大小，以检查抑郁症患者的消极情绪水平是否也存在差异，这表明抑郁症患者的情绪环境不敏感。此外，在每个任务中，积极情绪的多种行为测量将提供一个跨测量领域的快感缺乏症的综合评估。该项目还将证明抑郁症快感缺乏症的哪些成分和措施对临床干预有反应，哪些仍然受损，表明它们可能作为抑郁症的内表型。我们将招募健康对照者和患有忧郁症、非典型或非亚型抑郁症的患者。在完成心理诊断访谈和自我报告特质和状态水平的享乐加工后，参与者将完成三个平衡任务。在其中一项任务中，他们将观看情绪图片，听情绪声音，以及与每种刺激效价相关的线索，以提供情绪反应的实验评估。他们的评分和身体对提示、图片和声音的反应将被记录下来，以评估他们对实际刺激的喜欢程度和想要这些刺激的程度（通过他们对提示的反应来衡量）。另外两项任务是评估在愉快的活动中缺乏快乐（喜欢）或兴趣（想要）。一种是衡量以努力为基础的工作获得奖励，是对参与者在奖励活动中享受（喜欢）和兴趣（想要）的实验性评估。另一组测试的是参与者在一个食欲评价条件反射任务中学习愉快联想的能力，在这个任务中，中性词汇与非常愉快或中性的图片配对。我们将邀请同样的参与者在他们最初的疗程三个月后回到我们的实验室，检查快感缺乏的哪些过程和措施对临床改善（特别是在快感缺乏症状方面）有反应，哪些在抑郁症缓解的参与者中仍然受损。后者是抑郁症内表型的候选者，可以用来识别有抑郁症风险的人，并在他们变得严重抑郁之前主动干预。

DESCRIPTION (provided by applicant): Anhedonia, or the lack of positive emotion, is a critical component of depression that is represented in various ways in diagnostic criteria. All forms of depression may involve a lack of interest or pleasure in activities, particularly when depressed patients are contrasted against healthy controls. Melancholic depression specifically entails additional deficits in mood reactivity to pleasant events, in contrast to atypical depression, in which mood reactivity to pleasant events is present. Consistent with NIMH's Strategic Objective 1, this application seeks to assess anhedonia in a theoretically coherent way and address deficits in wanting, liking, and learning in depression, with tasks designed to assess the varieties of anhedonic processing in depression. In each task, postauricular reflex and zygomatic EMG magnitudes during pleasant vs. neutral conditions will be assessed as measures of positive emotional processing. Startle blink and corrugator EMG magnitudes will be assessed to examine whether depressed patients also differ in their levels of negative emotion, indicating an emotion context insensitivity in depression. Furthermore, multiple behavioral measures of positive emotion will be taken in each task to provide a comprehensive assessment of anhedonia across measurement domains. This project will also demonstrate which components and measures of depressive anhedonia are responsive to clinical intervention and which remain impaired, suggesting they may serve as endophenotypes for depression. We will recruit healthy controls and patients with melancholic, atypical, or non-subtyped depression. After completing psychodiagnostic interviews and self-reports of trait and state levels of hedonic processing, participants will complete three counterbalanced tasks. In one task, they will view emotional pictures and listen to emotional sounds, along with cues associated with each stimulus valence, to provide an experimental assessment of mood reactivity. Their ratings and bodies' reactions to the cues, pictures, and sounds will be recorded to assess their levels of liking the actual stimuli and wanting those stimuli (as measured by their reactions to the cues). Two additional tasks assess lack of pleasure (liking) or interest (wanting) in pleasant activities. One measures effort-based work for rewards and is an experimental assessment of participants' enjoyment (liking) and interest (wanting) during a rewarding activity. The other measures participants' ability to learn pleasant associations in an appetitive evaluative conditioning task, in which neutral words are paired with highly pleasant or neutral pictures. We will invite the same participants back to our laboratory three months after their initial session to examine which processes and measures of anhedonia are responsive to clinical improvement (particularly in anhedonic symptoms) and which remain impaired in remitted depressed participants. The latter make candidates for endophenotypes of depression, which can be used to identify people at risk for depression and intervene proactively before they become acutely depressed.